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Selected AbstractsClinical outcome and IL-17, IL-23, IL-27 and FOXP3 expression in peripheral blood mononuclear cells of pollen-allergic children during sublingual immunotherapyPEDIATRIC ALLERGY AND IMMUNOLOGY, Issue 1-Part-II 2010Kaisa Nieminen Nieminen K, Valovirta E, Savolainen J. Clinical outcome and IL-17, IL-23, IL-27 and FOXP3 expression in peripheral blood mononuclear cells of pollen-allergic children during sublingual immunotherapy. Pediatr Allergy Immunol 2010: 21: e174,e184. © 2009 John Wiley & Sons A/S Induction of allergen-specific, tolerogenic, IL-10 and/or TGF-,-producing T-regulatory (Treg) cells that express transcription factor FOXP3 is considered as one of the key mechanisms of allergen-specific immunotherapy. However, little is known of the induction of FOXP3 expression in children during sublingual immunotherapy (SLIT). Recently, also, a novel subgroup of T-helper (Th) cells, the Th17 cells, secreting predominantly IL-17 (IL-17A), was identified. The expressions of IL-17 or the Th17-regulating cytokines IL-23 and IL-27 during SLIT are currently completely unexplored. This randomized, placebo-controlled dose-response study was performed to analyze the effects of SLIT on FOXP3, IL-17, IL-23, and IL-27 expressions in peripheral blood mononuclear cells (PBMC) of children with allergic rhinitis and their associations with clinical outcome. Thirty children were included: ten received SLIT with a glycerinated mixture of birch, hazel and alder with a cumulative weekly dose of 24,000 SQ-U, 10 with dose 200,000 SQ-U/wk, and ten received placebo. Cytokine and FOXP3 mRNA expressions in allergen-, purified protein derivative-stimulated and non-stimulated PBMC were determined at 0, 1 and 2 yr of SLIT by real-time RT-PCR (TaqMan®). Symptoms and medications were recorded using diary cards. Allergen-induced IL-17 mRNA expression was significantly increased in the study subjects with elevated combined Symptom Medication Score (SMS) after 2 yr. There was also a significant positive correlation between the allergen-induced IL-17 and SMS in whole study group (r = 0.38, p = 0.039) and especially the 200,000 SQ-U dose-treated group (r = 0.74, p = 0.027) at 2 yr. Allergen-induced FOXP3 mRNA expression was significantly increased in the 200,000 SQ-U dose-treated children after two study years as compared with baseline (p = 0.016) and placebo-treated children (p = 0.028). The changes in FOXP3 mRNA expression positively correlated with IL-10 and TGF-, mRNAs during SLIT in whole study population. Increased allergen-induced IL-17 responses during SLIT are associated with elevated SMS. Increased tolerogenic, allergen-specific Treg responses are also observed in children during SLIT. [source] Immunotherapy in children and adolescents with allergic rhinoconjunctivitis: a systematic reviewPEDIATRIC ALLERGY AND IMMUNOLOGY, Issue 3 2008Esther Röder Allergen-specific immunotherapy is one of the cornerstones of allergic rhinoconjunctivitis treatment. Since the development of non-invasive administration forms with better safety profiles, there is an increasing tendency to prescribe immunotherapy in youngsters. However, no overview is available on the efficacy of immunotherapy in all its different administration forms in youngsters. Therefore, we systematically reviewed randomized controlled trials (RCTs) to evaluate the effect of immunotherapy with inhalant allergens on symptoms and medication use in children and adolescents with allergic rhinoconjunctivitis. Medline, EMBASE, the Cochrane Controlled Clinical Trials Register and reference lists of recent reviews and published trials were searched. RCTs including youngsters aged 0,18 yr with allergic rhinoconjunctivitis and comparing immunotherapy with placebo, symptomatic treatment or a different administration form of immunotherapy were included. Primary outcome measures were rhinoconjunctivitis symptom and/or medication scores. Methodological quality was assessed using the validated Delphi list. A method of best evidence synthesis, a rating system with levels of evidence based on the overall quality and the outcome of the trials, was used to assess efficacy. Six subcutaneous (SCIT), four nasal (LNIT), seven oral (OIT) and 11 sublingual (SLIT) immunotherapy trials, comprising 1619 youngsters, were included. Only 39% of the trials were of high methodological quality. For the SCIT and OIT subgroups the level of evidence for efficacy was conflicting. Moderate evidence of effect was found for LNIT. Analysis of the SLIT subgroup showed no evidence of effect. The evidence for the perennial and seasonal allergen trials within the subgroups varied from moderate evidence of effect to no evidence of effect. In conclusion, there is at present insufficient evidence that immunotherapy in any administration form has a positive effect on symptoms and/or medication use in children and adolescents with allergic rhinoconjunctivitis. [source] Efficacy and safety of subcutaneous immunotherapy with a biologically standardized extract of Ambrosia artemisiifolia pollen: a double-blind, placebo-controlled studyCLINICAL & EXPERIMENTAL ALLERGY, Issue 9 2004C. Mirone Summary Background The allergological relevance of Ambrosia in Europe is growing but the efficacy of the injective immunotherapy for this allergen has been documented only in Northern America. Objective We sought to study the safety and efficacy of injective immunotherapy in European patients sensitized to Ambrosia artemisiifolia. Methods Thirty-two patients (18 M/14 F, mean age 36.78, range 23,60 years) suffering from rhinoconjunctivitis and/or asthma and sensitized to Ambrosia were enrolled and randomized in a double-blind, placebo-controlled (DBPC) study lasting 1 year. A maintenance dose corresponding to 7.2 ,g of Amb a 1 was administered at 4-week intervals after the build-up. During the second and the third year, all patients were under active therapy in an open fashion. Symptom and medication scores, skin reactivity to Ambrosia (parallel line biological assay), and pollen counts were assessed throughout the trial. Results Twenty-three patients completed the trial. No severe adverse event was observed. During the DBPC phase, actively treated patients showed an improvement in asthmatic symptoms (P=0.02) and drug (P=0.0068) scores days with asthmatic symptoms (P=0.003), days with rhinitis symptoms (P=0.05), and days with intake of drugs (P=0.0058), as compared to before therapy. No improvement for any of these parameters was detected in the placebo group. Moreover, the number of days with rhinitis and asthma was significantly higher in the placebo as compared to the active group (P=0.048 and P<0.0001, respectively). Patients who switched from placebo to active therapy improved in rhinoconjunctivitis, asthma, and drug intake. The skin reactivity decreased significantly (12.2-fold, P=0.0001) in the active group whereas a slight increase (1.07-fold, P=0.87) was observed in the placebo group after the DBPC phase. After switching to active therapy, patients previously under placebo showed a significant decrease of this parameter (4.78-fold, P=0.002). Conclusion Injective immunotherapy is safe and clinically effective in European patients sensitized to Ambrosia. [source] Effects of high-dose sublingual immunotherapy on quality of life in patients with cypress-induced rhinitis: a placebo-controlled studyCLINICAL & EXPERIMENTAL ALLERGY REVIEWS, Issue 3 2006V. Di Rienzo Summary The efficacy of specific immunotherapy and particularly of sublingual immunotherapy (SLIT) in subjects allergic to Cupressaceae pollen is well defined, but no study assessed its effects on quality of life (QoL). We evaluated the effectiveness of SLIT with a standardized, high-dose extract of Juniperus ashei in patients with cypress-induced rhinitis, using QoL as the major outcome measure. Thirty-four patients, 20 males and 14 females, mean age 33.8 years, with allergic rhinitis (AR) from cypress pollen were randomly assigned to receive an allergen extract standardized in index of reactivity (IR) of J. ashei (19 patients) or a placebo (15 patients). The schedule was pre-coseasonal, with a build-up phase in 12 days and a maintenance treatment with 300 IR a day up to the end of the cypress pollen season. All patients registered in diary cards their symptoms, drug consumption and side-effects. The QoL was measured before and after SLIT by the Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) by Juniper during the peak of the cypress pollen season. QoL significantly improved in respect to baseline in actively (P=0.017) but not in placebo-treated patients, and there was a significant difference in favour of actively treated patients during the pollen season (P=0.02). Actively and placebo-treated patients had comparable symptom,medication scores in the period from 15 February to 15 March, corresponding to the peak pollen season, but placebo-treated patients showed an uneven drug consumption compared with actively treated patients. Side-effects were relatively common, but mostly with local short-lasting symptoms, and no systemic reaction was reported. These findings show that SLIT with high doses of J. ashei in subjects with cypress-induced rhinitis significantly improves QoL and confirm previous observations on the disagreement between QoL , which assesses patient's perception , and medical parameters used in trials. [source] T cell responses induced by allergen-specific immunotherapyCLINICAL & EXPERIMENTAL IMMUNOLOGY, Issue 1 2010E. Maggi Summary Allergen-specific immunotherapy is recognized as a highly effective practice in the treatment of patients with severe allergic rhinitis and/or asthma and is recommended by World Health Organization as an integrated part of allergy management strategy. Several studies have shown that allergen-specific immunotherapy, based on the administration of increasing doses of allergen, achieves a hyposensitization and reduces both early and late responses occurring during the natural exposure to the allergen itself. This is the unique antigen-specific immunomodulatory treatment in current use for human diseases. Successful immunotherapy is associated with reductions in symptoms and medication scores and improved quality of life. After interruption it usually confers long-term remission of symptoms and prevents the onset of new sensitizations in children up to a number of years. Subcutaneous immunotherapy usually suppresses the allergen-induced late response in target organs, likely due to the reduction of the infiltration of T cells, eosinophils, basophils, mast cells and neutrophils. In addition to the reduction of cells of allergic inflammation, immunotherapy also decreases inflammatory mediators at the site of allergen exposure. This review provides an update on the immunological T cell responses induced by conventional subcutaneous and sublingual immunotherapy, and gives a unifying view to reconciling the old dualism between immunoredirecting and immunoregulating mechanisms. 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